To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug...To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.展开更多
AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate th...AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.展开更多
This study aimed to seek necrosis avid agents with high safety from DNA binding agents.The interaction of 5-hydroxytryptophan(5-HTP)with DNA was investigated by a series of spectroscopic studies.Then,5-HTP was labeled...This study aimed to seek necrosis avid agents with high safety from DNA binding agents.The interaction of 5-hydroxytryptophan(5-HTP)with DNA was investigated by a series of spectroscopic studies.Then,5-HTP was labeled with iodine-131([^(131)I]5-HTP)and the necrosis avidity of[^(131)I]5-HTP was evaluated by in vitro cell binding assays,in vivo biodistribution experiments and blocking experiment.Finally,the potential of[^(131)I]5-HTP to image necrotic myocardium was explored in rat models with myocardial infarction by SPECT/CT imaging.Results showed that 5-HTP bound to DNA in groove binding mode and the binding constant was 1.69×10~4 L/mol.[~(^(131))I]5-HTP showed specific affinity to necrotic A549 cells,which might be related to cell nucleus.Biodistribution and autoradiography results showed preferential accumulation of[^(131)I]5-HTP in necrotic muscle(necrotic/viable muscle ratio:6.95?0.68 at 3 h postinjection(p.i.)),which could be blocked by 5-HTP with 66.7%decline,indicating that[^(131)I]5-HTP might share the same necrotic targets with 5-HTP.On SPECT/CT images,a hotspot was clearly observed at 3h p.i.in the necrotic myocardium while not in the control myocardium.In conclusion,[^(131)I]5-HTP is a novel necrosis avid agent and can rapidly visualize necrotic myocardium at 3 h p.i.The necrosis avidity mechanism of[^(131)I]5-HTP may be attributed to its interactions with exposed DNA in the necrotic tissues.展开更多
基金National Natural Science Foundation of China (Grant No. 30570653)National Basic Research Program of China (Grant No. 2003CB515400)985 Program of China Ministry of Education
文摘To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.
基金Supported by The Natural Science Foundation of Guangdong,No.S2012040006557
文摘AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.
基金partially supported by the National Natural Science Foundation of China(Nos.81473120,81501536,81473120)
文摘This study aimed to seek necrosis avid agents with high safety from DNA binding agents.The interaction of 5-hydroxytryptophan(5-HTP)with DNA was investigated by a series of spectroscopic studies.Then,5-HTP was labeled with iodine-131([^(131)I]5-HTP)and the necrosis avidity of[^(131)I]5-HTP was evaluated by in vitro cell binding assays,in vivo biodistribution experiments and blocking experiment.Finally,the potential of[^(131)I]5-HTP to image necrotic myocardium was explored in rat models with myocardial infarction by SPECT/CT imaging.Results showed that 5-HTP bound to DNA in groove binding mode and the binding constant was 1.69×10~4 L/mol.[~(^(131))I]5-HTP showed specific affinity to necrotic A549 cells,which might be related to cell nucleus.Biodistribution and autoradiography results showed preferential accumulation of[^(131)I]5-HTP in necrotic muscle(necrotic/viable muscle ratio:6.95?0.68 at 3 h postinjection(p.i.)),which could be blocked by 5-HTP with 66.7%decline,indicating that[^(131)I]5-HTP might share the same necrotic targets with 5-HTP.On SPECT/CT images,a hotspot was clearly observed at 3h p.i.in the necrotic myocardium while not in the control myocardium.In conclusion,[^(131)I]5-HTP is a novel necrosis avid agent and can rapidly visualize necrotic myocardium at 3 h p.i.The necrosis avidity mechanism of[^(131)I]5-HTP may be attributed to its interactions with exposed DNA in the necrotic tissues.
